Myotonic Dystrophy Type 1 and Type 2Phase 3MINDNCT04700046
Study to Investigate the Efficacy and Safety of Mexiletine in Patients With Myotonic Dystrophy Type 1 and Type 2
A Phase 3 study testing Mexiletine 167 mg in people with Myotonic Dystrophy Type 1 and Type 2, run by Lupin Ltd..
Trial summary
A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Investigate the Efficacy and Safety of Mexiletine During 26 Weeks of Treatment in Patients with Myotonic Dystrophy Type 1 and Type 2 [The MIND Study] Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myotonic Dystrophy Type 1 and Type 2
- What is being tested?
- Mexiletine 167 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 3 Sep 2021to 12 Aug 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- DM1 or DM2 diagnosis confirmed genetically;
- Ability to provide informed consent;
- Ability to understand the study requirements including intention to stay in the study until the end-of-study visit at 26 weeks of treatment;
- Male or non-pregnant female ≥18 years of age;
- Female patients of childbearing potential must be using an acceptable form of birth control as determined by the investigator (e.g., oral contraception, implantable, injectable/transdermal hormonal contraception, intrauterine device (IUD), barrier methods), tubal ligation, have a vasectomized partner, or are practicing abstinence;
- No significant cardiac abnormalities as determined by a cardiologist's assessment of the electrocardiogram (ECG) and echocardiogram;
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- Capable of swallowing capsules;
- Have sufficient finger flexor strength to grasp the handle of the dynamometer used to measure myotonia;
- Presence of clinical handgrip myotonia (delayed relaxation of grip of ≥ 3 seconds after maximum voluntary contraction) at screening;
- Have a Day 1 (pre-dose) handgrip dynamometer mean relaxation time of ≥1.5 seconds for the force to decline from 90% of maximum voluntary contraction force to 5%;
- Be able to walk independently 10 meters (cane, walker, orthoses allowed);
- DM1 patients only - Muscular impairment rating scale (MIRS) score of 2, 3, or 4.
Who cannot join
- Are pregnant or lactating;
- Have any one of the following medical conditions: uncontrolled diabetes mellitus, cancer other than skin cancer less than five years previously (e.g., basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) of skin allowed), multiple sclerosis, seizure disorders, or other serious medical illness;
- Severe renal impairment (glomerular filtration rate (GFR) < 30 mL/min);
- Medical conditions which could interfere with muscle function such as infections, trauma, fractures, or planned surgery;
- Medical conditions that could affect hand functioning including but not limited to rheumatoid arthritis, Dupuytren's contracture, hand deformity, etc.;
- Severe arthritis or other medical condition (besides DM1/DM2) that would significantly impact ambulation;
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- High incidence of falls or fall-associated fractures (>5 falls during the past 12 months);
- Preexisting elevated liver function tests > 3 times the upper limit of normal (ULN) at screening (alanine transaminase (ALT)/aspartate transaminase (AST), gamma-glutamyl transferase (GGT)) and/or any abnormal chemistry, hematology or urine lab considered clinically significant by the investigator;
- Treatment with mexiletine within 4 weeks prior to baseline (Day 1);
- Intake of any anti-myotonic treatment within 4 weeks prior to baseline (Day 1) such as propafenone, flecainide, lamotrigine, carbamazepine or any other channel-blocker/ anticonvulsive drugs;
- Use of any concomitant medications that could increase the cardiac risk;
- Known allergy to mexiletine or any local anesthetics;
- Participation in another interventional clinical study during the last 3 months;
- Wheelchair-bound or bed-ridden;
- Any cardiac safety-associated condition including any of the following criteria detected by screening cardiac evaluations including 24-hour Holter monitoring, ECG, echocardiogram and clinical evaluations:
- PR interval ≥240 ms or QRS duration ≥120 ms on resting ECG
- Personal history of 3rd degree or 2nd degree type 2 atrioventricular block or sinus node dysfunction with pauses ≥3 seconds
- Personal history of sustained atrial fibrillation, flutter or tachycardia (duration >30 seconds)
- Personal history of non-sustained (ventricular triplets or more) or sustained ventricular tachycardia
- Myocardial infarction (acute or past) or coronary artery stenosis >50%
- New York Heart Association (NYHA) Class II to IV heart failure
- Left ventricular systolic dysfunction with ejection fraction <50%
- Sinus node dysfunction (including ECG sinus rate <50 beats per minute (BPM))
- Co-administration of mexiletine and antiarrhythmics inducing torsades de pointes (class Ia: quinidine, procainamide, disopyramide, ajmaline; class Ic: encainide, flecainide, propafenone, moricizine; class III: amiodarone, sotalol, ibutilide, dofetilide, dronedarone, vernakalant)
- Patients with implantable cardioverter defibrillators (ICDs) and pacemakers are excluded
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Investigate the Efficacy and Safety of Mexiletine During 26 Weeks of Treatment in Patients With Myotonic Dystrophy Type 1 and Type 2 [The MIND Study]
A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Investigate the Efficacy and Safety of Mexiletine During 26 Weeks of Treatment in Patients with Myotonic Dystrophy Type 1 and Type 2 [The MIND Study]
Read the detailed description
This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled study intended to evaluate the safety and efficacy of mexiletine in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2). The study will consist of a 4-week screening period and a 26-week treatment phase with patient visits as screening, baseline, weeks 1, 2, 6, 14, 18, and 26. Eligible patients will be randomized to mexiletine or placebo in a 1:1 ratio. Approximately 158 DM1 patients (79 active: 79 placebo) are planned to be enrolled across 10-15 experienced investigational centers in Europe. In addition, up to 16 DM2 patients are planned to be enrolled (sub-group - 8 active: 8 placebo).
Study drug (mexiletine 167 mg or placebo) will be started as a once a day (QD) treatment regimen. The dose will be titrated up at the Week 1 and Week 2 visits to a maximum of 1 capsule three times a day. Depending on tolerability, the dose can also be either maintained or - if required - reduced by one dose step at any time during the study to a minimum dose of 167 mg QD.
- Conditions
- Myotonic Dystrophy Type 1 and Type 2
- Being tested
- Mexiletine 167 mg, Placebo
- Medical subject headings
- Myotonic Dystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mexiletine 167 mgDrug
Mexiletine 167 mg (equivalent to mexiletine HCl 200 mg) immediate release, oral capsules.
PlaceboDrug
The placebo capsules contain the same ingredients as the active formulation with the exception of mexiletine
| Study group | Role | What they receive |
|---|---|---|
| Mexiletine | Active comparator | Mexiletine 167 mg (equivalent to mexiletine HCl 200 mg) Receives: Drug: Mexiletine 167 mg |
| Placebo | Placebo comparator | The placebo capsules contain the same ingredients as the active formulation with the exception of mexiletine Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the efficacy and safety of mexiletine for the symptomatic treatment of myotonia
To assess the efficacy and safety of mexiletine for the symptomatic treatment of myotonia in adult patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2) by handgrip relaxation time in DM1 patients: Mean change from baseline (i.e., Day 1, pre-dose) in relaxation time of handgrip after 3 seconds of MVIC of the dominant hand using a handgrip dynamometer at Week 26. Mean relaxation time at each timepoint will be calculated from the first contraction in each of the 3 trials (each trial consists of 6 maximal voluntary contractions). Relaxation time for the assessment of myotonia will be calculated as the time required for the force to decline from 90% of maximum voluntary contraction force to 5%.
Measured: 6 months
Secondary outcomes (8)
To assess the efficacy of mexiletine on patient-reported outcomes by way of standardized instrument for measuring generic health status, EuroQol- 5 Dimension (EQ-5D).
The EQ-5D is a multi-attribute utility instrument for measuring health-related quality of life. EQ-5D: EuroQol - 5 dimensions (Health-related quality of life measure developed by EuroQol group). The index score is calculated by software hence minimum/maximum or better/worse not applicable. The EQ-5D assessments will be collected on Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation).
Measured: Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)
To assess the efficacy of mexiletine on patient-reported outcomes by Timed "Up & Go" (TUG)
The TUG Test (Podsiadlo, 1991; Trip 2009a) measures, in seconds, the time taken by an individual to stand up from a standard arm chair (approximate seat height of 46 cm, arm height 65 cm), walk a distance of 3 meters (approximately 10 feet), turn, walk back to the chair, and sit down.
Measured: 6 months
To assess the efficacy of mexiletine on patient-reported outcomes by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) overall
INQoL- Individualized neuromuscular quality of life questionnaire. Higher score represents worsening and lower score represents better. Minimum/maximum- not applicable. The INQoL overall questionnaire will be completed on Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)
Measured: Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)
To assess the efficacy of mexiletine on functional capacity outcome measures by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) locking domain.
To assess the efficacy of mexiletine on functional capacity outcome measures by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) locking domain.INQoL- Individualized neuromuscular quality of life questionnaire. Higher score represents worsening and lower score represents better. Minimum/maximum- not applicable.
Measured: 6 months
To assess the efficacy of mexiletine on functional capacity outcome measures by Myotonia Behavior Scale (MBS).
MBS was originally developed by Budzynski, Stoyva, Adler and Mullaney as a pain measurement instrument (Budzynski, 1973). The patient chooses one out of six framed sentences, which most closely describe the impact of the stiffness on everyday life. MBS: myotonia behavior scale, score ranges 0 - 5. Lower score is better and higher score is worsening. The MBS assessments will be completed on Day 1 (pre-dose), Week 2, Week 6, Week 14, Week 18, and Week 26 (or early discontinuation)
Measured: Day 1 (pre-dose), Week 2, Week 6, Week 14, Week 18, and Week 26 (or early discontinuation)
To assess the efficacy of mexiletine on functional capacity outcome measures by Visual Analog Scale (VAS) for myotonia.
The construction of VAS in this study is an absolute measure, with a straight, horizontal, 10 cm line having the endpoints "No stiffness at all" and "Stiffness as worst possible". The patient responds with a score on the line to the nearest millimeter on a 100-point scale. The VAS will be completed on Day 1 (pre-dose), Week 2, Week 6, Week 14, Week 18, and Week 26 (or early discontinuation)
Measured: 6 months
To assess the efficacy of mexiletine on functional capacity outcome measures by 10 meter Walk Test (10mWT).
the 10mWT is a performance-based test assessing walking in two different conditions, own preferred speed and maximum speed, over a short distance. The time taken to walk 10 meters at usual comfortable and maximum speed is recorded with a stopwatch.
Measured: 6 months
To assess the efficacy of mexiletine on functional capacity outcome measures by DM1-Active-c.
DM1-Activ-c scale is a disease-specific, Rasch-built scale, developed as a patient-reported outcome measure of capacity for activity and social participation with a 0-100 interval range (a higher score indicates higher capacity) (Hermans, 2015).VAS- Visual analogue scale. Score ranges 0-100. Lower is better and higher is worsening. The DM1-Activ-c scale score will be collected on Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)
Measured: Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2021
- Study start3 Sep 2021
- Primary completion1 Jul 2024 (estimated)
- Study completion12 Aug 2024 (estimated)
Why it stopped: Assessing novel alternative study designs and regulatory pathways
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myotonic Dystrophy Type 1 and Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lupin Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04700046
- Sponsor's protocol ID
- MEX-DM-301
- Acronym
- MIND
- Status last verified
- May 2024
- First submitted
- 5 Jan 2021
- Last updated
- 6 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Investigate the Efficacy and Safety of Mexiletine During 26 Weeks of Treatment in Patients With Myotonic Dystrophy Type 1 and Type 2 [The MIND Study]
- ClinicalTrials.gov ID
- NCT04700046
- Acronym / sponsor ID
- MIND / MEX-DM-301
- Conditions
- Myotonic Dystrophy Type 1 and Type 2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Assessing novel alternative study designs and regulatory pathways
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Lupin Ltd.Industry (pharma, biotech, devices)
- Study start
- 3 Sep 2021 (actual)
- Primary completion
- 1 Jul 2024 (estimated)
- Study completion
- 12 Aug 2024 (estimated)
- First posted
- 7 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Investigate the Efficacy and Safety of Mexiletine During 26 Weeks of Treatment in Patients with Myotonic Dystrophy Type 1 and Type 2 [The MIND Study]
Detailed description
This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled study intended to evaluate the safety and efficacy of mexiletine in patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2). The study will consist of a 4-week screening period and a 26-week treatment phase with patient visits as screening, baseline, weeks 1, 2, 6, 14, 18, and 26. Eligible patients will be randomized to mexiletine or placebo in a 1:1 ratio. Approximately 158 DM1 patients (79 active: 79 placebo) are planned to be enrolled across 10-15 experienced investigational centers in Europe. In addition, up to 16 DM2 patients are planned to be enrolled (sub-group - 8 active: 8 placebo).
Study drug (mexiletine 167 mg or placebo) will be started as a once a day (QD) treatment regimen. The dose will be titrated up at the Week 1 and Week 2 visits to a maximum of 1 capsule three times a day. Depending on tolerability, the dose can also be either maintained or - if required - reduced by one dose step at any time during the study to a minimum dose of 167 mg QD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mexiletine | Active comparator | Drug: Mexiletine 167 mgMexiletine 167 mg (equivalent to mexiletine HCl 200 mg) |
| Placebo | Placebo comparator | Drug: PlaceboThe placebo capsules contain the same ingredients as the active formulation with the exception of mexiletine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- DM1 or DM2 diagnosis confirmed genetically;
- Ability to provide informed consent;
- Ability to understand the study requirements including intention to stay in the study until the end-of-study visit at 26 weeks of treatment;
- Male or non-pregnant female ≥18 years of age;
- Female patients of childbearing potential must be using an acceptable form of birth control as determined by the investigator (e.g., oral contraception, implantable, injectable/transdermal hormonal contraception, intrauterine device (IUD), barrier methods), tubal ligation, have a vasectomized partner, or are practicing abstinence;
Key exclusion criteria (25 listed)
- Are pregnant or lactating;
- Have any one of the following medical conditions: uncontrolled diabetes mellitus, cancer other than skin cancer less than five years previously (e.g., basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) of skin allowed), multiple sclerosis, seizure disorders, or other serious medical illness;
- Severe renal impairment (glomerular filtration rate (GFR) < 30 mL/min);
- Medical conditions which could interfere with muscle function such as infections, trauma, fractures, or planned surgery;
- Medical conditions that could affect hand functioning including but not limited to rheumatoid arthritis, Dupuytren's contracture, hand deformity, etc.;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mexiletine 167 mgMexiletine 167 mg (equivalent to mexiletine HCl 200 mg) immediate release, oral capsules. | Drug | Mexiletine |
| PlaceboThe placebo capsules contain the same ingredients as the active formulation with the exception of mexiletine | Drug | Placebo |
Primary outcome
Assess the efficacy and safety of mexiletine for the symptomatic treatment of myotonia
Time frame: 6 months
To assess the efficacy and safety of mexiletine for the symptomatic treatment of myotonia in adult patients with myotonic dystrophy type 1 and type 2 (DM1 and DM2) by handgrip relaxation time in DM1 patients: Mean change from baseline (i.e., Day 1, pre-dose) in relaxation time of handgrip after 3 seconds of MVIC of the dominant hand using a handgrip dynamometer at Week 26. Mean relaxation time at each timepoint will be calculated from the first contraction in each of the 3 trials (each trial consists of 6 maximal voluntary contractions). Relaxation time for the assessment of myotonia will be calculated as the time required for the force to decline from 90% of maximum voluntary contraction force to 5%.
8 secondary outcomes
To assess the efficacy of mexiletine on patient-reported outcomes by way of standardized instrument for measuring generic health status, EuroQol- 5 Dimension (EQ-5D).
Time frame: Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)
To assess the efficacy of mexiletine on patient-reported outcomes by Timed "Up & Go" (TUG)
Time frame: 6 months
To assess the efficacy of mexiletine on patient-reported outcomes by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) overall
Time frame: Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)
To assess the efficacy of mexiletine on functional capacity outcome measures by Individualized Neuromuscular Quality of Life Questionnaire (INQoL) locking domain.
Time frame: 6 months
To assess the efficacy of mexiletine on functional capacity outcome measures by Myotonia Behavior Scale (MBS).
Time frame: Day 1 (pre-dose), Week 2, Week 6, Week 14, Week 18, and Week 26 (or early discontinuation)
To assess the efficacy of mexiletine on functional capacity outcome measures by Visual Analog Scale (VAS) for myotonia.
Time frame: 6 months
To assess the efficacy of mexiletine on functional capacity outcome measures by 10 meter Walk Test (10mWT).
Time frame: 6 months
To assess the efficacy of mexiletine on functional capacity outcome measures by DM1-Active-c.
Time frame: Day 1 (pre-dose), Week 14, and Week 26 (or early discontinuation)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mexiletine 167 mg in people with Myotonic Dystrophy Type 1 and Type 2, run by Lupin Ltd..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 May 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the efficacy and safety of mexiletine for the symptomatic treatment of myotonia (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2024.